Using the human neuroblastoma as a model sysem, we are studying the molecular events associated with the development of pediatric tumors. Of special interest is identification and characterization of the molecular events important for the regulation of tissue specific differentiation and the arrest of growth which invariably accompanies it. In this regard, ongoing work is focused on testing the hypothesis that amongst histologically indistiguishable solid tumors there are different genetic entities which correspond to cells at different stages in the differentiation of the tissue in which a tumor arises. Such a schema has been hypothesized for both lymphoid and hematopietic malignancies in which specific markers of differentiation have been extensively characterized. During the past year we have sought profiles of gene expession which distinguish amongst histopathologically identical tumors, and we are characterizing the relationship of these different tumor types to different stages in the differentiation of the peripheral nervous system. Experiments to determine whether genetically similar tumors have a homogeneous and predictble biologic behavior are also being pursued. We plan to extend these studies to central nervous systems tumors also.